Department of Traditional Chinese Medicine, Shanghai Pudong New Area Zhoupu Hospital, Shanghai, 201318, People's Republic of China.
Department of Hepatobiliary Surgery, The First Hospital of Yulin City, Yulin, 719000, Shaanxi, People's Republic of China.
Biol Res. 2018 May 30;51(1):14. doi: 10.1186/s40659-018-0163-x.
Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism.
The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot.
In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, β-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3.
Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/β-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.
神经激肽 1（NK1）受体在肿瘤的发展中起着至关重要的作用。然而，作为 NK1 受体拮抗剂的 NKP608 是否对结直肠癌细胞的耐药性有影响尚不清楚。因此，在本研究中，我们研究了 NKP608 对人结直肠癌细胞的作用，并探讨了其潜在的机制。
通过细胞计数试剂盒-8（CCK8）检测结直肠癌细胞的增殖，通过 Transwell 检测细胞迁移和侵袭，通过 Annexin V-荧光素异硫氰酸酯/碘化丙啶染色和流式细胞术检测细胞凋亡率。通过 Western blot 检测分子机制的参与。
在这项研究中，我们发现 NKP608 抑制了 HCT116 细胞的增殖、迁移/侵袭。此外，NKP608 降低了 Wnt-3a、β-catenin、Cyclin D1 和血管内皮生长因子（VEGF）的表达，同时诱导了 E-钙黏蛋白的表达。此外，流式细胞术分析表明 NKP608 诱导了 HCT116 细胞的凋亡，Western blot 检测凋亡相关蛋白表明 NKP608 下调了 Bcl-2，同时上调了 Bax 和活性 Caspase-3。
综上所述，我们的结果表明，NKP608 通过抑制 Wnt/β-catenin 信号通路抑制结直肠癌细胞的增殖、迁移和侵袭。因此，NKP608 可能代表一种有前途的结直肠癌治疗药物。
